MP31-01 FUNCTIONAL MRNA - MICRORNA REGULATORY MODULES IDENTIFIED USING COMPREHENSIVE MOLECULAR CHARACTERIZATION OF BLADDER OUTLET OBSTRUCTION

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 2015MP31-01 FUNCTIONAL MRNA - MICRORNA REGULATORY MODULES IDENTIFIED USING COMPREHENSIVE MOLECULAR CHARACTERIZATION OF BLADDER OUTLET OBSTRUCTION Katia Monastyrskaya, Ali Hashemi Gheinani, Hubert Rehrauer, Catharine Aquino Fournier, Irene Keller, Rémy Bruggmann, and Fiona C. Burkhard Katia MonastyrskayaKatia Monastyrskaya More articles by this author , Ali Hashemi GheinaniAli Hashemi Gheinani More articles by this author , Hubert RehrauerHubert Rehrauer More articles by this author , Catharine Aquino FournierCatharine Aquino Fournier More articles by this author , Irene KellerIrene Keller More articles by this author , Rémy BruggmannRémy Bruggmann More articles by this author , and Fiona C. BurkhardFiona C. Burkhard More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1356AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder outlet obstruction (BOO) results in profound structural and functional changes in the detrusor, including hypertrophy and bladder decompensation (fibrosis). Previously we determined miRNA profiles characteristic of defined states of BOO in human patients and used bioinformatic prediction of their target genes to identify the regulated signalling pathways. Here we present the mRNA transcriptome analysis of the same samples and correlate microRNA and mRNA regulation patterns in order to validate functional ontology. METHODS Controls, BOO with and without detrusor overactivity (OAB and BOO groups, respectively) and acontractile bladders (AC group) were defined by urodynamics in human subjects. Bladder dome biopsies were collected and RNA isolated using mirVANA kit for miRNA. mRNA sequencing (mRNA-seq) method was used for gene expression profiling of BOO stages (4 groups, n = 6 per group). The Enrichment analysis using GeneGo MetaCore software was applied to the significantly altered mRNAs. Functional analysis of a network identified the most significant biological functions of the genes in the network. RESULTS In agreement with our previous miRNA sequencing data, mRNA sequencing data revealed clustering of the normal bladder samples with the samples of BOO with detrusor overactivity; whereas samples of BOO without overactivity were clustered with acontractile bladder samples. Pathway analysis showed 9 common pathways within the first 100 top most significantly regulated for 3 defined states of bladder dysfunction, and the most relevant biological processes activated in all were TGF-beta, WNT and cytoskeletal remodelling; regulation of EMT and cytoskeletal remodelling via Rho-GTPases. Within the top 50 pathways, OAB and BOO shared 6 pathways, mostly cytoskeleton remodelling, WNT and TGF-beta, whereas AC and BOO shared 19 immune response-specific pathways. These data correlate well with the earlier pathway analysis based on miRNA profiling: we confirmed that miR-212/132 cluster activates calcineurin/NFATC and RCAN1 (mRNA up-regulated 2.8 and 6 times, respectively) and that up-regulation of HIF1alpha and VEGFA mRNAs, indicative of hypoxia, induces miR-34c. CONCLUSIONS This is the first report indicating that different states of bladder outlet obstruction have specific miRNA and mRNA profiles. Our work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of lower urinary tract dysfunction. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e355 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Katia Monastyrskaya More articles by this author Ali Hashemi Gheinani More articles by this author Hubert Rehrauer More articles by this author Catharine Aquino Fournier More articles by this author Irene Keller More articles by this author Rémy Bruggmann More articles by this author Fiona C. Burkhard More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...